Combination Antibody Therapy Reduces Relapsed Multiple Myeloma

Sanofi recently announced that when Sarclisa (isatuximab), a monoclonal antibody, is added to carfilozomib and dexamethasone, it reduces the risk of relapsed multiple myeloma progression or death in patients compared to standard care.

“In the Phase 3 IKEMA trial, the addition of Sarclisa to carfilzomib and dexamethasone reduced the risk of disease progression or death by 47 percent compared to treatment with carfilzomib and dexamethasone alone,” Philippe Moreau, MD, department of hematology, University Hospital of Nantes, France, said in the announcement. 

“These results suggest the potential of Sarclisa to become a new standard of care in the relapsed multiple myeloma setting.”

The randomized, open label Phase 3 IKEMA clinical trial enrolled 302 patients with relapsed multiple myeloma. 

Sarclisa was administered at a dose of 10mg once weekly for four weeks and then every other week for 28-day cycles, researchers noted. These doses were in combination with carfilzomib twice weekly at the 20/56mg and dexamethasone at the standard dose for the duration of treatment.

The trial found that Sarclist combination therapy met trial primary endpoint at the pre-planned interim analysis. Carfilzomib and dexamethasone (Kd) saw a median progression free survival (PFS) of 19.15 months. 

Interim results will be released on June 14 during the European Hematology Association (EHA) Virtual Congress (EHA25), Sanofi said.

Despite available treatments, multiple myeloma remains an incurable malignancy and is associated with significant patient burden, Sanofi said. Since the disease does not have a cure, most patients will relapse.

Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death and immunomodulatory activity.

Researchers noted that the safety and tolerability of Sarclisa observed in this trial was consistent with the observed safety profile of Sarclisa in other clinical trials, with no new safety signals observed.

“This is the second Phase 3 trial to demonstrate superior results with Sarclisa combination therapy over a standard of care regimen, adding to the growing body of evidence that our anti-CD38 monoclonal antibody has the potential to make a meaningful difference for patients,” said John Reed, MD, PhD, global head of research and development at Sanofi. 

“We believe Sarclisa has the potential to become the anti-CD38 of choice for the treatment of multiple myeloma. We look forward to seeing the results from future clinical trials to understand the impact of Sarclisa in earlier stages of disease.”

Secondary endpoints for the IKEMA trial included overall response rate (ORR), complete response (CR), very good partial response (VGPR), and minimal residual disease (MRD).

The study found no statistically significant difference in ORR, which remained similar for each arm at 86.6 percent for the Sarclisa combination versus 82.9 percent for Kd. 

The rate of CR was 39.7 percent in the Sarclisa combination arm and 27.6 percent in the Kd arm, while the rate of VGPR was 72.6 percent for patients receiving Sarclisa combination therapy and 56.1 percent for patients receiving Kd, researchers noted. 

MRD-negative complete response was seen in 29.6 percent of patients in the Sarclisa combination arm, compared to 13 percent of patients in the Kd arm. 

Adverse events were also noted. Over 75 percent of patients treated with Sarclisa combination therapy reported adverse events, versus 67.2 percent of patients treated with Kd. 

Additionally, respiratory infections were seen in 32.2 percent of patients in the Sarclisa combination therapy arm versus 23.8 percent of patients in the Kd arm.